What is the management for nephritis?

Management of Nephritis

The management of nephritis should be guided by the specific type and class of nephritis, with lupus nephritis being the most well-studied form requiring a combination of immunosuppressive therapy and supportive care based on histological classification.

Diagnosis and Assessment

• Kidney biopsy is essential when there is evidence of kidney involvement, especially with persistent proteinuria ≥0.5 g/24 hours or unexplained decrease in GFR 1
• Biopsy should be classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system 1
• Assessment should include:
  • Activity and chronicity indices
  • Thrombotic and vascular lesions associated with antiphospholipid antibodies
  • Tubulointerstitial changes

Treatment of Lupus Nephritis by Class

Class III or IV (±V) Lupus Nephritis (Proliferative)

1. Initial Treatment:

   • First-line options:

     • Mycophenolic acid (MPA/MMF) at target dose 2-3 g/day for 6 months 1
     • OR Low-dose intravenous cyclophosphamide (CY) (500 mg every 2 weeks for a total of 6 doses) 1
     • PLUS Glucocorticoids: IV methylprednisolone pulses (500-2500 mg total dose) followed by oral prednisone (0.3-0.5 mg/kg/day), tapered to ≤7.5 mg/day by 3-6 months 1

   • Alternative for high-risk patients (with crescents, fibrinoid necrosis, or severe interstitial inflammation):

     • High-dose intravenous CY (0.5-0.75 g/m² monthly for 6 months) 1
     • OR MMF + calcineurin inhibitor (especially tacrolimus) for patients with nephrotic-range proteinuria 1

2. Maintenance Treatment:

   • MMF/MPA (1-2 g/day) or azathioprine (2 mg/kg/day) 1
   • Low-dose prednisone (2.5-5 mg/day) if needed 1
   • Continue for at least 3-5 years in complete clinical response 1

Class V Lupus Nephritis (Membranous)

1. Initial Treatment:

   • MMF (target dose 2-3 g/day) + glucocorticoids 1
   • Alternative options: intravenous CY or calcineurin inhibitors (especially tacrolimus) 1

2. Maintenance Treatment:

   • Similar to class III/IV maintenance
   • Consider calcineurin inhibitors at lowest effective dose 1

Adjunctive Treatments for All Classes

• Hydroxychloroquine (5 mg/kg/day, adjusted for GFR) for all patients unless contraindicated 1
• ACE inhibitors or ARBs for all patients with UPCR >500 mg/g or hypertension 1
• Statins based on lipid levels and cardiovascular risk 1
• Bone protection (calcium/vitamin D supplementation) 1
• Consider acetylsalicylic acid (80-100 mg/day) if antiphospholipid antibodies are positive 1
• Consider anticoagulation for nephrotic syndrome with serum albumin <20 g/L 1

Management of Refractory Disease

For patients failing to achieve treatment goals:

1. Evaluate possible causes including adherence and drug levels 1
2. Treatment options:
   • Switch from MMF to CY or vice versa 1
   • Consider rituximab (1000 mg on days 0 and 14) 1
   • Consider belimumab as add-on treatment 1

Monitoring

• Schedule visits every 2-4 weeks during the first 2-4 months after diagnosis or flare 1

• Monitor at each visit:

  • Body weight and blood pressure
  • Estimated GFR and serum albumin
  • Proteinuria (UPCR or 24-hour collection)
  • Urinary red cell count or sediment
  • Complete blood count
  • Complement levels (C3/C4) and anti-dsDNA antibodies 1

• Treatment targets:

  • Reduction in proteinuria by at least 25% at 3 months
  • Reduction in proteinuria by at least 50% at 6 months
  • UPCR target below 500-700 mg/g by 12 months 1

• Consider repeat kidney biopsy for:

  • Worsening kidney function
  • Non-responsiveness to treatment
  • Relapse to assess histologic changes 1

Special Considerations

Pregnancy Planning

• Pregnancy may be planned when LN is stable and inactive (UPCR <500 mg/g for 6 months, GFR >50 mL/min) 1
• Compatible medications (hydroxychloroquine, prednisone, azathioprine, calcineurin inhibitors) should be continued 1
• MMF/MPA should be withdrawn at least 3-6 months before conception 1

End-Stage Kidney Disease

• All methods of kidney replacement therapy can be used 1
• Transplantation may be preferred when extra-renal lupus is inactive for at least 6 months 1

Common Pitfalls to Avoid

1. Delayed diagnosis: Regular monitoring of patients with SLE is crucial as kidney involvement can be asymptomatic
2. Inadequate immunosuppression: Underdosing or premature discontinuation increases risk of flares
3. Excessive glucocorticoid exposure: Use pulse therapy and rapid tapering to minimize toxicity
4. Neglecting supportive care: ACE inhibitors/ARBs and hydroxychloroquine are essential components
5. Premature switching of therapy: Patients with nephrotic-range proteinuria may require 12-18 months to achieve complete response 1
6. Overlooking drug toxicity: Monitor for specific adverse effects of immunosuppressants
7. Ignoring non-adherence: Assess medication adherence in cases of treatment failure

The management of nephritis requires careful histological assessment and a tailored approach based on disease class, severity, and individual patient factors to optimize outcomes and minimize treatment-related complications.